SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients
NCT ID: NCT02117167
Last Updated: 2024-01-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
999 participants
INTERVENTIONAL
2014-04-23
2023-12-31
Brief Summary
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Detailed Description
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New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing).
Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met : stable or responding disease has been observed after 4 cycles of chemotherapy (investigator judgment) and targetable alteration has been identified by the Molecular tumor board (MTB).
If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 4 cycles of a platinum-based chemotherapy AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor \[low tumor cells percentage, technical issue during genomic analysis, etc.\], or a non-inclusion criteria that precluded entry into the substudy 1)
Randomization phase:
The mandatory post-chemotherapy 28-day wash-out period following cycle 4 of chemotherapy will provide time to achieve all the required tests and examinations.
The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy:
Substudy 1 : targeted therapies versus standard maintenance therapy
* Arm A1 / targeted arm: targeted maintenance from a list of 6 targeted drugs guided by the genomic analysis, or
* Arm B1 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).
Substudy 2 : immunotherapy versus standard maintenance therapy
* Arm A2 / immunotherapy maintenance arm: MEDI4736 or
* Arm B2 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Substudy 1: targeted agent
Arm A1/ targeted arm: targeted maintenance from a list of targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, olaparib tablet per os 300 mg bd continuous dosing savolitinib tablet per os 600 mg od continuous dosing
AZD2014
Target: m-TOR
AZD4547
Target: FGFR
AZD5363
Target: AKT
AZD8931
Target: HER2, EGFR
Selumetinib
Target: MEK
Vandetanib
Target : VEGF, EGFR
savolitinib
target : MET
Olaparib
target : PARP
Substudy 1: standard maintenance therapy
Arm B1/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice
Standard maintenance for squamous NSCLC
Pemetrexed
Standard maintenance for non squamous NSCLC
Substudy 2: Immunotherapy
Arm A2/ Immunotherapy arm: maintenance with durvalumab for patient without actionable genomic alterations or non eligible to Targeted substudy 1, durvalumab Intra-venous 10 mg/kg, Q2W
Durvalumab
Target: PD-L1
Substudy 2: standard maintenance therapy
Arm B2/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice
Standard maintenance for squamous NSCLC
Pemetrexed
Standard maintenance for non squamous NSCLC
Interventions
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AZD2014
Target: m-TOR
AZD4547
Target: FGFR
AZD5363
Target: AKT
AZD8931
Target: HER2, EGFR
Selumetinib
Target: MEK
Vandetanib
Target : VEGF, EGFR
Standard maintenance for squamous NSCLC
Pemetrexed
Standard maintenance for non squamous NSCLC
Durvalumab
Target: PD-L1
savolitinib
target : MET
Olaparib
target : PARP
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Metastatic relapse or stage IV at diagnosis, or stage IIIb not amenable to surgery or radiotherapy
* No EGFR-activating mutation or ALK translocation
* primary tumor or metastases that can be biopsied, excluding bone.
* Age \>18 years
* WHO Performance Status 0/1
* Chemo-naïve patients eligible to a first line platinum-based chemotherapy
* No tumor progression observed with the current line of treatment
* measurable target lesion or evaluable diseases RECIST
* Patients who received 4 cycles of an induction platinum-based chemotherapy and who have a SD or a PR at randomization
* presenting at least one genomic alteration from the predefined list
* Age \> 25 years for patients planned to receive AZD4547
* 28-day washout period from chemo prior to randomization and grade ≤1 residual toxicities
* Patients who received 4 cycles of an induction platinum-based chemotherapy and who have a SD or a PR at randomization
* Patients not eligible to substudy 1
* 28-day washout period from chemo prior to randomization and grade ≤1 residual toxicities
Exclusion Criteria
* Abnormal coagulation contraindicating biopsy
* Inability to swallow
* Major problem with intestinal absorption
* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
* Any factors increasing the risk of QTc prolongation or arrhythmic events
* Experience of any of the following in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, past or current uncontrolled angina pectoris, congestive heart failure NYHA Grade ≥2, torsades de pointes, current uncontrolled hypertension, cardiomyopathy
* Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which requires steroid treatment or any evidence of clinically interstitial lung disease
* Previous or current malignancies of other histologies within the last 5 years,
* Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
* Diagnosis of diabetes mellitus type I or II
* diagnosis of acne rosacea, severe psoriasis and severe atopic eczema
* Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone
* History of retinal degenerative disease, eye injury or corneal surgery in the previous 3 months, past history of central serous retinopathy or retinal vein occlusion, intraocular pressure \>21 mmHg, or uncontrolled glaucoma.
* History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
* Renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome, renal tubular acidosis
* Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450
Randomized phase:
Substudy 1:
* Life expectancy \<3 months
* Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinum-based chemotherapy before 4 full cycles have been delivered
* Less than 28 days from radiotherapy, less than 2 weeks from palliative radiation
* Patients previously treated with a targeted agent in the same class as agents tested in this study
* Toxicities of grade ≥2 from any previous anti-cancer therapy
* Altered haematopoietic or organ function
* Mean resting corrected QT interval (QTc) \>480msec (or QTcF \>450 msec) obtained from 3 consecutive ECGs
* Left ventricular ejection fraction (LVEF) \<55% (MUGA scan or Echocardiogram),
* Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with AZD4547 orAZD8931 or Selumetinib
* Patients using non-substitutable drugs, that are known to prolong QT interval or induce Torsades de Pointes, when they are supposed to be treated with vandetanib, AZD5363 or AZD8931
Substudy 2:
* Life expectancy \<3 months
* Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinum-based chemotherapy before 4 full cycles have been delivered
* Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
* Toxicities of grade ≥2 from any previous anti-cancer therapy
* Altered haematopoietic or organ function
* Mean resting QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 consecutive ECGs using Bazett's Correction
* Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
* Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
* History of primary immunodeficiency
18 Years
ALL
No
Sponsors
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Intergroupe Francophone de Cancerologie Thoracique
OTHER
Fondation ARC
OTHER
AstraZeneca
INDUSTRY
UNICANCER
OTHER
Responsible Party
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Principal Investigators
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Fabrice BARLESI, Pr
Role: PRINCIPAL_INVESTIGATOR
CHU Hopital Nord Marseille
Locations
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Centre Hospitalier Henri Duffau
Avignon, , France
Centre Hospitalier Universitaire de Besancon - Hopital Jean Minjoz
Besançon, , France
Hôpital Avicenne
Bobigny, , France
Institut Bergonié
Bordeaux, , France
Hôpital Ambroise Paré
Boulogne-Billancourt, , France
Hospices Civils de Lyon- Hôpital Louis Pradel
Bron, , France
Centre François Baclesse
Caen, , France
CHU Caen
Caen, , France
Chu de Caen - Hopital Cote de Nacre
Caen, , France
Hôpital Louis Pasteur
Chartres, , France
centre Jean Perrin
Clermont-Ferrand, , France
CHU Clermont Ferrand - Hôpital Gabriel Montpied
Clermont-Ferrand, , France
Hopitaux Civils de Colmar
Colmar, , France
Centre Hopsitalier Intercommunal de Créteil
Créteil, , France
Centre Georges François Leclerc
Dijon, , France
CHU Grenoble
Grenoble, , France
Chd Vendee
La Roche-sur-Yon, , France
CH du Mans
Le Mans, , France
Centre Oscar Lambret
Lille, , France
CHRU de Lille
Lille, , France
Centre Léon Bérard
Lyon, , France
Hôpital Nord
Marseille, , France
Institut Paoli Calmettes
Marseille, , France
Institut de cancérologie de l'Ouest
Nantes, , France
Centre Antoine Lacassagne
Nice, , France
Chr Orleans
Orléans, , France
AH-HP Hôpital Saint Louis
Paris, , France
AP-HP Hôpital Cochin
Paris, , France
AP-HP Hôpital Tenon
Paris, , France
Institut Curie
Paris, , France
Centre Hospitalier de Pau
Pau, , France
Centre Hospitalier Lyon Sud
Pierre-Bénite, , France
Chru Strasbourg - Nouvel Hopital Civil
Strasbourg, , France
CHI de Toulon - Hôpital Sainte-Musse
Toulon, , France
CHU Toulouse -Hôpital Larrey
Toulouse, , France
Hôpital Bretonneau
Tours, , France
Gustave Roussy
Villejuif, , France
Countries
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References
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Middleton G, Crack LR, Popat S, Swanton C, Hollingsworth SJ, Buller R, Walker I, Carr TH, Wherton D, Billingham LJ. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer. Ann Oncol. 2015 Dec;26(12):2464-9. doi: 10.1093/annonc/mdv394. Epub 2015 Sep 25.
Related Links
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Unicancer official website
Intergroupe Francophone de Cancérologie Thoracique (IFCT) official website
SAFIR01 study results
Other Identifiers
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2013-001653-27
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
UC-0105/1305 / IFCT 1301
Identifier Type: -
Identifier Source: org_study_id
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